18.417: lecture 2
Brute force and digest problems
instructor: Ross A. Lippert
http://www-math.mit.edu/~lippert/18.417/
| For class:Problem set 1 is out |  |
Restriction enzyme

Restriction enzyme animation
Enzyme activity works to destroy foreign DNA

Restriction enzymes galore

Gel-electrophoresis
Lengths of DNA fragments can be measured:
animated demo
Fragments after radioactive of florescent staining

Restriction mapping
The goal in restriction mapping is be able to find the order of the fragments, knowing just the fragment lengths. |  |
Restriction mapping problems
Full restriction digest |  |
Partial restriction digest |  |
A formal statement of the Partial Digest Problem
- Idea: a piece of DNA is digested by a restriction enzyme, resulting in a multiset of fragments, one fragment per pair of restriction sites.
- Idealizations: we can control digestion enough to guarantee that every possible fragment will be produced, and we can count the multiplicity of fragments of with the same length.
- Input: a multiset of fragments resulting from the ideal partial digestion of a piece of DNA.
- Output: a set of restriction site locations and endpoints which gives rise to the same multiset of fragments.
Example:
input: L = {3,5,5,8,9,14,14,17,19,22}
output: X = {0,5,14,19,23}, endpoints at 0 and 23 with sites at 5,14,19.
digestion: | | 0 | 5 | 14 | 19 | 22 | | 0 | | 5 | 14 | 19 | 22 | | 5 | | | 9 | 14 | 17 | | 14 | | | | 5 | 8 | | 19 | | | | | 3 | | 22 | | | | | |
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Word of warning: multiple solutions
The two sets {0,1,2,5,7,9,12} and {0,1,5,7,8,10,12} digest to the same thing
| 0 | 1 | 2 | 5 | 7 | 9 | 12 | | 0 | | 1 | 2 | 5 | 7 | 9 | 12 | | 1 | | | 1 | 4 | 6 | 8 | 11 | | 2 | | | | 3 | 5 | 7 | 10 | | 5 | | | | | 2 | 4 | 7 | | 7 | | | | | | 2 | 5 | | 9 | | | | | | | 3 | | 12 | | | | | | | |
| | 0 | 1 | 5 | 7 | 8 | 10 | 12 | | 0 | | 1 | 5 | 7 | 8 | 10 | 12 | | 1 | | | 4 | 6 | 7 | 9 | 11 | | 5 | | | | 2 | 3 | 5 | 7 | | 7 | | | | | 1 | 3 | 5 | | 8 | | | | | | 2 | 4 | | 10 | | | | | | | 2 | | 12 | | | | | | | |
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The multiset {1,1,2,2,2,3,3,4,4,5,5,5,6,7,7,7,8,9,10,11,12}
The Double Digest Problem
- Idea: an easier laboratory experiment is to digest the same DNA with two different enzymes, resulting in 3 fragment sets.
- Idealizations: still requires that we can know the multiplicity of fragments of with the same length.
- Input: 3 multisets of fragments resulting from the ideal double digestion of a single piece of DNA.
- Output: a set of restriction site locations and endpoints for the two enzymes, which gives rise to the same multisets of fragments.
Sites A = {173,201,315,512,526,526,557,619,776,777}
Sites B = {71,91,159,250,258,273,371,413,558,640}
- A fragments = {28,114,197,14,0,31,62,157,1}
- B fragments = {20,68,91,8,15,98,42,145,82}
- A+B fragments = {20,68,14,28,49,8,15,42,56,42,99,14,0,31,1,61,21,136,1}